A 67-Year-Old Woman With Neck And Shoulder Pain

Correct Answer: B

The patient shows nonspecific symptoms of rheumatological type stiffness most severe in the morning along with similarly nonspecific constitutional symptoms of weeks to months duration. An initial sedimentation rate certainly drew the physicians off the scent, but with time, the working diagnosis—polymyalgia rheumatica (PMR)—finally comes into clearer focus.

As the symptomatology evolved, the presence of proximal bilateral girdle pain and reduced range of motion was revealed and repeat inflammatory markers started elevating. Based on those symptoms, a diagnosis of PMR was secured. This is not an unusual situation, wherein retrospectively the diagnosis of PMR seemed obvious yet required weeks to months to secure prospectively.

Treatment and management. A repeat sedimentation rate was 92 mm/hour. Rheumatoid factors were absent. Ultrasonography was performed within the week and demonstrated the presence of biceps tenosynovitis and subacromial bursitis bilaterally. Corticosteroids in the form of prednisone 20 mg/d were initiated with significant relief of symptoms within the first week and essentially total clinical resolution after 1 month. Sedimentation rate was 55 mm/hour at 3 weeks and 28 mm/hour at 6 weeks. Tapering was initiated after 8 weeks, using a 2.5 mg dosage decrement monthly.

Discussion. The typical epidemiology of PMR involves a patient population that is generally White/Northern European, older than 50 years of age, and predominantly female.¹ The index case is thus a perfect fit. Genetics and abnormal immune responses (post-viral, post-vaccines) are under suspicion, but no bona fide etiology has yet to be defined.

Regarding the diagnosis, there still is no specific laboratory marker for PMR. Generally, a high sedimentation rate in the 80-100 range can lead to anemia or inflammation. In serious and late diagnosis situations, an overlap into giant cell arteritis with headaches in the temporal region and even vision loss if ophthalmic arteries could occur.

Although perhaps 95% of cases will involve the shoulder girdle, involvement of the neck and pelvic girdles can also be targeted.¹ Our patient experienced weeks of neck pain and stiffness of severe nature resulting in detailed, costly, and time-consuming evaluations before her symptomatology evolved into other areas and her sedimentation rate blossomed into a PMR diagnosis. An important clinical clue here is the presence of bilaterality. Many orthopedic and neurologic differential diagnoses (cervical disc disease, migraine syndromes) will remain unilateral, whereas PMR almost always is or becomes bilateral.^1,2

Regarding laboratory studies, the inflammatory markers of sedimentation rate of greater than 40 and usually much higher and/or C-reactive protein (CRP) greater than 6 mg/dL remain hallmarks of support for the diagnosis.^1-3

Although atypical, as was seen in our case, the initial inflammatory markers may be normal, but as stated, they essentially always evolve. So it needs to be said that a single (early) normal sedimentation rate and CRP should not exclude the diagnosis in a patient with suggestive symptoms. Conversely, a very high sedimentation rate and CRP is not diagnostic for PMR because a host of other rheumatologic syndromes (rheumatoid arthritis or spondyloarthritis, for example) will manifest similar high levels.¹ Thus, answer A is not correct.

A relatively new finding in PMR diagnosis utilizes ultrasonography. Without diving too deeply into the specifics of and arguments for/against types of ultrasound evaluation, in summary it seems the most specific finding is the presence of subacromial bursitis, either unilateral or bilateral, which alone have a sensitivity of 66-80% and specificity of 68-89%.^1,3 The American College of Rheumatology guidelines award a diagnosis point in their scheme for PMR diagnosis when these ultrasound studies are positive and create an increase the specificity of their scheme from 81.5% to a very fine 91.3%.^1,3 This makes answer B the best choice here.

In summary then, we use typical epidemiologic and clinical symptomology to suspect the diagnosis and can follow with classical blood inflammatory markers of sedimentation rate and CRP with the newer ultrasound evaluation demonstrating widespread inflammatory bursitis and tenosynovitis, especially the subacromial joints, to arrive at an accurate diagnosis of PMR.

Once a firm diagnosis is in hand, quite effective therapeutics are available. Initial therapy can be done in a primary setting with more secondary lines best handled by rheumatologic consultation. A basic overview follows.

The main pedestal of therapy in PMR, and the universally used initial modality is corticosteroids. Dosage and duration are less clear. It is an old and still accepted clinical aphorism that quite small dosages (10 to 15 mg/d of oral prednisone) have a rapid (measured in days) and high incidence of response. Typical initial dosage regimens are between 10-20 mg/d with high percentages of improved clinical symptoms within 2 weeks (and quite often far quicker) and with normalization of sedimentation rate/CRP within 4 weeks. Duration is determined clinically with initial dosage being maintained for 4 weeks after resolution of symptoms undertaken. The use of the word slow should not be taken lightly as one review notes that “typical treatment lasts 1-2 years”.^1,4

If and when the initial response is either absent or the ongoing steroid dosage required is excessive (> 20-25 mg/d) the accepted secondary therapy is the addition of methotrexate, another oral agent, in starting dosages of 10-15 mg weekly. A similar strategy is suggested for patients who experienced relapses after steroid therapy.^2,4 The data for methotrexate (MTX) is somewhat mediocre, but MTX is the next option after steroids in several large PMR society guides.^2,4

Finally, a comment of the use of biologics, specifically IL-6 blocking agents. The theory is attractive and efficacy has been demonstrated in small studies but far larger, blinded, randomized studies need to be performed before becoming standard of care.⁵ These biologic agents require parenteral administration and add an exponential increment in toxicity potential and cost and remain in the clinical research realm for now. Answers C and D are not appropriate at this time.

Patient follow-up. She currently is taking 10 mg/daily with excellent clinical/sedimentation rate control and will begin the final phases of taper (1 mg/week every 4-8 weeks). She is approximately 8 months from diagnosis and initiation of therapy. Her PMR scoring algorithm had a value of 7 at onset and likely 8 at the time of definitive diagnosis and initiation of therapy. Scoring algorithm for classifying PMR.²

What’s the Take Home?

Polymyalgia rheumatica is an inflammatory disorder of as yet unknown cause with demographics showing White, Northern European, 50 years of age or older, and female predominance. Classical symptomology is morning stiffness, pain, and reduced range of motion most prominent in the morning and involving proximal shoulder, hip, and neck girdle areas. Most patients will eventually manifest marked elevations in the inflammatory markers of sedimentation rate/CRP but will not have rheumatoid factor positivity. Newer radiologic techniques of ultrasound have found the presence of subacromial bursitis, which adds specificity and sensitivity to the clinical diagnosis. A scoring schema is available to aid in the diagnosis.

The backbone of therapy is a steroid regimen, usually 20 mg/d prednisone for several months followed by a very slow taper. Resistant cases and relapses can be treated by the addition of oral methotrexate with good effect, and more novel anti-inflammatory modalities such as IL-6 blockers are still being studied.